long-term functional outcomes and patient perspective following altered fractionation radiotherapy...
TRANSCRIPT
ORIGINAL ARTICLE
Long-term Functional Outcomes and Patient PerspectiveFollowing Altered Fractionation Radiotherapy with ConcomitantBoost for Oropharyngeal Cancer
Bena Cartmill • Petrea Cornwell • Elizabeth Ward •
Wendy Davidson • Sandro Porceddu
Received: 12 June 2011 / Accepted: 21 January 2012 / Published online: 24 February 2012
� Springer Science+Business Media, LLC 2012
Abstract With no long-term data available in published
research to date, this study presents details of the swal-
lowing outcomes as well as barriers to and facilitators
of oral intake and weight maintenance at 2 years after
altered fractionation radiotherapy with concomitant boost
(AFRT-CB). Twelve patients with T1–T3 oropharyngeal
cancer who received AFRT-CB were assessed at baseline,
6 months, and 2 years post-treatment for levels of dys-
phagia and salivary toxicity, food and fluid tolerance,
functional swallowing outcomes, patient-reported function,
and weight. At 2 years, participants were also interviewed
to explore barriers and facilitators of oral intake. Outcomes
were significantly worse at 2 years when compared to
baseline for late toxicity, functional swallowing, and
patient-rated physical aspects of swallowing. Most patients
(83%) tolerated a full diet pretreatment, but the rate fell to
42% (remainder tolerated soft diets) at 2 years. Multiple
barriers to oral intake that impacted on activity and
participation levels were identified. Participants lost 11 kg
from baseline to 2 years, which was not regained between
6 months and 2 years. Global, social, and emotional
domains of patient-reported function returned to pretreat-
ment levels. At 2 years post AFRT-CB, worsening salivary
and dysphagia toxicity, declining functional swallowing,
and multiple reported ongoing barriers to oral intake had a
negative impact on participants’ activity and participation
levels relating to eating. These ongoing deficits contributed
to significant deterioration in physical swallowing func-
tioning determined by the MDADI. In contrast, patients
perceived their broader functioning had improved at
2 years, suggesting long-term adjustment to ongoing
swallowing deficits.
Keywords Deglutition � Deglutition disorders �Long-term outcomes � Altered fractionation radiotherapy �Oropharynx � Squamous cell carcinoma
Introduction
Treatment intensification with altered fractionation radio-
therapy (AFRT) for head and neck cancer (HNC) has
demonstrated improved locoregional control and overall
survival compared with conventionally fractionated radio-
therapy [1]. Despite this benefit, AFRT treatment has been
associated with increased acute toxicity of greater severity
and longer duration [2, 3]. The presence of dysphagia and
mucositis has been identified in the literature as persisting
B. Cartmill (&)
Division of Speech Pathology and Speech Pathology
Department, The University of Queensland and Princess
Alexandra Hospital, Ipswich Road, Woolloongabba, Brisbane,
QLD 4102, Australia
e-mail: [email protected]
P. Cornwell
Griffith Health Institute and Metro North Health Service District,
Griffith University and Queensland Health, Mt Gravatt,
Brisbane, QLD 4111, Australia
E. Ward
Division of Speech Pathology and Centre for Functioning and
Health Research, The University of Queensland and Queensland
Health, Buranda, Brisbane QLD 4102, Australia
W. Davidson
Dietetics Department, Princess Alexandra Hospital,
Woolloongabba, QLD 4102, Australia
S. Porceddu
Radiation Oncology Department and School of Medicine,
Princess Alexandra Hospital and The University of Queensland,
Woolloongabba, Brisbane, QLD 4102, Australia
123
Dysphagia (2012) 27:481–490
DOI 10.1007/s00455-012-9394-0
in the early phase after treatment with AFRT [4–8]. Acute
toxicity such as mucositis and pain has been associated
with deteriorating functional outcomes known to impact on
swallowing and mastication [9], resulting in a large pro-
portion of patients requiring modified diets and nutritional
supplementation [10, 11].
Currently, there is minimal information available about
the extent to which dysphagia and associated toxicities
persist long term in the AFRT population. Based on radio-
biological principles, late radiation effects are dependent on
the total dose and the dose per fraction, with larger fraction
sizes increasing the risk of severe late effects [4, 12]. Hence,
as a consequence of the reduced dose per fraction used in
accelerated radiotherapy regimens, late toxicity rates for
necrosis, xerostomia, laryngeal edema, skin, and subcuta-
neous toxicity have been found to be significantly less for
accelerated regimens compared with conventional counter-
parts post-treatment [7, 8]. It is possible then that dysphagia
and associated toxicities may also be less severe in the long
term. However, to what extent late effects exist and continue
to impact on swallowing, nutrition, and patient-rated func-
tion at 2 years following AFRT is currently unknown.
Generally, research examining radiotherapy treatment
protocols has indicated that patient-reported function post-
treatment is on an upward trajectory, with the lowest point
immediately after treatment and improving to pretreatment
levels within 1 year [13–18]. Whether this same pattern is
evident following AFRT requires further investigation, as
few studies to date have employed longitudinal study
designs that extend to 2 years or more post-treatment. The
preliminary data currently available would suggest that
significant improvements in dysphagia and functional
swallowing status can be anticipated in the long term [10,
11]. Eighteen percent of a heterogeneous HNC population
that received AFRT required alternative feeding due to
dysphagia 1–2 months post-treatment [11]. However, by
12 months post-treatment this had improved, with only 7%
with ongoing significant dysphagia [11]. In a more recent
study of the impact of AFRT with a concomitant boost
(AFRT-CB) in a homogeneous group of patients with
oropharyngeal cancers, the current research team found
significant deterioration in functional swallowing, nutri-
tion, and patient-rated functional impact from pretreatment
to 6 weeks post-treatment, with some recovery by
6 months post-treatment but still below pretreatment levels
[10]. This pattern of improvement toward 6 months post-
treatment also concurs with previous research that exam-
ined quality of life (QoL) following a hyperfractionated
and accelerated radiotherapy protocol (dose/fraction size
\1.5–1.6 Gy) and found improved outcomes at 6 and
12 months post-treatment compared to baseline [18]. Such
data would tend to suggest that there are ongoing
improvements in swallowing function, swallowing-related
toxicity, and in patient perspectives of function, which may
be evident in the longer term.
Following conventional, hypofractionated, and com-
bined modality radiotherapy treatments for HNC, studies
have shown that long-term treatment-related side effects
impact on swallowing and nutrition, which affects QoL and
causes distress up to a decade post-treatment [19–22].
Consequently, as part of understanding the full impact of
AFRT on the individual, it is important that the extent of
any persistent late effects following AFRT treatment and
the potential impact of these effects on patient function are
better understood. To this end, the aims of the current study
were to (1) examine the functional swallowing, nutritional
status, and general and swallowing-related patient-rated
function at 2 years post-treatment with AFRT-CB for
locally advanced oropharyngeal cancer, and (2) further
explore the patient’s perspective of his/her ongoing side
effects and barriers to oral intake at 2 years post-AFRT.
Materials and Methods
Participants
Participants were drawn from the Multidisciplinary Head
and Neck Clinic at the Princess Alexandra Hospital,
Brisbane, Australia, following diagnosis of a T1–T3 locally
advanced squamous cell carcinoma (SCC) of the orophar-
ynx [base of tongue, tonsil, pharyngeal wall, or supraglottis
(within 1 cm of the oropharynx)]. Eligible participants
were those who commenced treatment with AFRT-CB with
curative intent during a 33-month period ending in August
2009. The AFRT-CB regimen involved elective sites being
treated to 50 Gy at 2 Gy/day over 5 weeks. Known sites of
disease received a concomitant boost to a total of 66 Gy
over 5 weeks with an afternoon boost dose (with a mini-
mum of 6 h between doses) of 1.6 Gy/day in weeks 4 and
5. Ineligible patients were those recommended for surgical
or multimodal treatment or those who had a previous
diagnosis of oropharyngeal SCC or any other medical
condition that may have affected long-term swallowing
function (i.e., neurological or neurodegenerative disease).
Any patient who developed in-field recurrence or sub-
sequent neurological or neurodegenerative disease after
completing treatment up until 2 years post-treatment was
also excluded. All patients received their treatment at the
Metro South Radiation Oncology Service in Brisbane,
Australia. This research was approved by the Human
Research and Ethics Committees at the Princess Alexandra
Hospital, Australia, and The University of Queensland, and
all participants consented to involvement in the study.
The cohort was drawn from that previously reported by
Cartmill et al. [10]. Seventeen patients were recommended
482 B. Cartmill et al.: Long-term Functional Outcomes and Patient Perspective
123
for treatment with AFRT-CB, and all were eligible for
recruitment. Of those, 15 participants consented to partic-
ipate but only 12 were eligible to complete all aspects
required for this study. One participant died during treat-
ment of causes unrelated to cancer, and two participants
died between 6 months and 2 years post-treatment: one due
to local recurrence and postoperative complications and the
other from causes unrelated to the cancer diagnosis.
Analysis was conducted on the 12 participants who were
eligible for follow-up at 2 years post-treatment. The mean
age at presentation was 66 years (range = 53–82 years,
SD = 20.3) and 83% of participants were male (Table 1).
The majority presented with tonsillar primaries and node-
negative neck disease and 50% had T2 disease. One third
of the participants had stage III disease, and one quarter
each had stage II and stage IV disease. The majority (67%)
were current or ex-smokers and 92% were current drinkers
(n = 11).
Procedure
The current study used a mixed methodology design to
explore both patterns of change across time and detailed
information of current swallowing status at 2 years post-
AFRT. This methodology involved collection of toxicity
ratings, current dietary tolerance, weight, and patient-rated
swallowing and general function at baseline, 6 months, and
again at 2 years post-treatment. To further examine the
patient’s perspective of swallowing and nutrition function
at 2 years post-treatment, each participant was contacted
via phone to complete a semistructured interview.
At baseline, 6 months, and 2 years post-treatment, spe-
cific toxicity information regarding dysphagia and xero-
stomia was collected using the relevant adverse event (AE)
subscales of the Common Toxicity Criteria of Adverse
Events version 3 (CTCAE v3). These subscales form part
of the total CTCAE tool, a comprehensive, multimodal
toxicity grading schedule that scores both acute and late
AEs in oncology [23]. With this tool dysphagia is rated on
a 5-point scale (grade 1 = mild, grade 2 = moderate,
grade 3 = severe, grade 4 = life-threatening or disabling,
and grade 5 = death related to AE) and xerostomia on a
3-point scale (grade 1 = mild, grade 2 = moderate, grade
3 = severe) as this AE is not considered life-threatening or
to cause death. Toxicity ratings were completed by the
participant’s radiation oncologist.
At each time point dietary tolerance was determined
based on clinical assessment and patient report of food and
fluids consumed regularly as part of their dietary routine.
Patient descriptions of their regular food and fluid consis-
tencies were subsequently recoded consistent with the
terminology of the Australian national standards [24] for
foods (full, soft, minced, pureed, or liquid only) and fluids
(thin, mildly thick, moderately thick, and extremely thick).
This information and other clinical indicators reported by
the patient were used to score functional swallowing out-
come with the Royal Brisbane Hospital Outcome Measure
for Swallowing (RBHOMS) [25]. The RBHOMS measures
everyday performance of swallowing function using a
10-part outcome measure scale [25]. This scale is clinically
valid and responsive to changes in swallowing function
over time and has high levels of sensitivity and specificity
and high interrater reliability [25]. The scale is divided into
four stages of swallowing function: (1) nil by mouth, (2)
commencing oral intake, (3) establishing oral intake, and
(4) maintaining oral intake. Each stage is further divided
into levels that are described with specific clinical features
allowing clinicians to differentiate between ten specific
ratings of swallow function.
At baseline and 6 months post-treatment, weight was
collected to the nearest 0.1 kg using a digital scale (G-Tech
International GL-6000). Weight was recorded at the same
Table 1 Demographic details
of AFRT-CB cohort at
presentation
a L = left, R = rightb Information regarding alcohol
history not reported
Participant No. Age Sex TNM classification and locationa Stage Smoking Alcohol
01 82 M T1N0 L pharyngeal wall I Ex Current
02 63 M T2N0 supraglottis II Current Current
03 79 M T3N0 BOT III Ex Current
04 72 M T2N0 L tonsil II Never Current
05 69 F T2N2b L tonsil IV Ex N/Ab
06 70 M T1N0 L tonsil I Ex Current
07 69 M T2N1 R tonsil III Ex Current
08 59 M T2N0 R supraglottis II Ex Current
09 59 M T1N2a R tonsil IV Never Current
10 58 F T3N0 R tonsil III Current Current
11 53 M T2N1 R tonsil III Never Current
12 54 M T1N2a R tonsil IV Never Current
B. Cartmill et al.: Long-term Functional Outcomes and Patient Perspective 483
123
location using the same scales throughout this study, with
the exception being at 2 years post-treatment, where
weight (in kg) was obtained through verbal patient report.
Patients completed the Functional Assessment of Cancer
Therapy Additional Concerns for Head and Neck Cancer
(FACT-H&N) [26] and the M. D. Anderson Dysphagia
Inventory (MDADI) [27] questionnaires at baseline, 6 months,
and 2 years post-treatment. These questionnaires were chosen
for their validity and reliability with the HNC population [26,
27]. General patient-perceived function was measured using the
FACT-H&N. Four core domains of patient-rated function are
assessed (physical, social/family, emotional, and functional
well-being) using 27 individual items. Twelve additional items
assess patient perceptions of treatment-related side effects
specifically for HNC [26, 28]. Patient-rated swallowing func-
tion was scored using the MDADI. The MDADI contains 20
items that are divided into global, emotional, functional, and
physical subscales and scored between 0 (extremely low
functioning) to 100 (extremely high functioning).
At the 2-year post-treatment time point only, an addi-
tional exploration of swallowing function was undertaken
using a semistructured patient interview. Interviews were
conducted via phone and the interviewer completed real-
time notations of patient responses. A series of questions
was used to stimulate discussion around three themes: (1)
the presence/absence of any ongoing side effects related to
treatment; (2) current swallowing, eating, and drinking
functions and any strategies used to improve oral intake;
and (3) current nutritional status (need for nutritional
supplements) and any strategies used to improve nutrition.
The interview took approximately 30 min to complete.
During the interview, opportunities were taken to clarify
and expand upon the content of responses with the patient
to ensure the nature of their reported side effects, and
current swallowing and nutrition statuses were accurately
recorded.
Data analysis
All quantitative data were entered into a Microsoft Excel
spreadsheet (Microsoft Corp., Redmond, WA, USA). Stata
ver. 10 for Mac (StataCorp., College Station, TX, USA) was
used for all statistical analyses. Descriptive measures,
including means and standard deviations, were recorded for
all outcome measures. Two analyses were conducted to
compare changes in the ordinal data collected for toxicity,
swallowing, and patient-rated functional impact: (1) change
in function from pretreatment to 2 years post-treatment and
(2) change in function from 6 months to 2 years post-treat-
ment. Nonparametric Wilcoxon signed-rank tests were used
for both analyses. Changes in diet and fluid consistencies
tolerated over time were measured using v2 tests. Paired
t tests were used to record change over time points for ratio
data (e.g. weight). For all statistical comparisons, p \ 0.05
was taken to indicate statistical significance.
Information obtained from the semistructured interviews
was collated by the interviewing clinician (BC), and the
patient descriptions of side effects and barriers to oral
intake were reported as frequency data. These data were
then subjected to secondary analysis, with each reported
side effect or barrier classified using the core set descrip-
tors from the World Health Organisation International
Classification of Functioning, Disability and Health (ICF)
core set for HNC [29, 30]. The ICF core set for HNC was
developed in consensus with 33 international experts and
includes 112 different ICF categories deemed relevant to
the specific disease condition of HNC [30]. Thirty-four
categories outline body functions, 33 body structures, 26
activities and participation, and 19 contextual environ-
mental factors. Analysis of patient responses using this
framework was used to gain a more holistic understanding
of the nature of functional swallowing and nutritional
outcomes experienced at 2 years after AFRT-CB. Patient
responses were coded across all relevant categories, e.g. a
reported presence of ‘‘dry mouth’’ was classified under a
body impairment of ‘‘salivation,’’ which resulted in an
activity limitation in ‘‘eating.’’ It is important to note that
exploration of contextual factors was not a focus of the
current study and was therefore not included in the
analysis.
Results
Analysis over time revealed a significant worsening in
xerostomia (salivary toxicity) and swallowing (dysphagia
toxicity) as per the CTCAE between pretreatment and
2 years post-treatment and between 6 months and 2 years
post-treatment (Table 2). Statistical comparisons revealed
that functional swallowing level (as scored by the
RBHOMS) at 2 years post-treatment was significantly
reduced in comparison to pretreatment and 6 months post-
treatment (Table 2). Change in functional swallowing
ability was not related to fluid intake as all participants
reported tolerating thin fluids at all time points. However,
food intake, as described by diet tolerance across time
points, ranged from a minced diet to a full/normal diet,
with the proportion of participants tolerating a full diet
changing over time. The majority of patients (83%) toler-
ated a full diet pretreatment, but this number decreased to
50% at 6 months post-treatment and to 42% at 2 years post-
treatment. At 6 months post-treatment the remaining 50% of
participants were managing a soft diet, while at 2 years post-
treatment 58% reported restricting their diet to softer con-
sistencies (i.e. avoiding hard, chewy, and dry solids). This
showed a trend toward significant decline over time
484 B. Cartmill et al.: Long-term Functional Outcomes and Patient Perspective
123
(v2 = 8.43, p = 0.08). Significant weight loss was observed
from pretreatment to 2 years post-treatment, with a mean
11 kg loss during this time. Weight did not change signifi-
cantly from 6 months to 2 years post-treatment (Table 2).
Analysis of patient-rated functional impact revealed that
between pretreatment and 2 years post-treatment, partici-
pants noted that there had been a significant negative
impact on their life within the physical domain of the
MDADI (Table 2). Between 6 months and 2 years post-
treatment there was significant improvement for the head
and neck–specific domain of the FACT-H&N; however,
there were no other significant findings between pretreat-
ment and 2 years post-treatment and between 6 months and
2 years post-treatment on either the MDADI or the FACT-
H&N (Table 2).
Outcomes of the semistructured interviews revealed that
participants reported 15 barriers to oral intake with varying
rates of frequency (Fig. 1). These barriers were able to be
classified into nine categories of body function impairment
using the comprehensive ICF core set for HNC. The most
common patient-reported impairments in bodily functions
were classified under salivation, energy and drive, taste
function, and pharyngeal swallow (Table 3). These
impairments in body function were also determined to have
an impact on the activity limitation and participation
restriction levels. All patient-reported barriers resulted in
activity limitations and participation restrictions in eating
(100%). A smaller proportion of patient-reported barriers
identified limitation and restrictions in looking after one’s
health (2/15) and carrying out daily routine (1/15)
(Table 3).
Participants were also probed regarding strategies that
facilitated the efficiency of their swallowing or their eating
and drinking experience (Fig. 2) and strategies to prevent
further weight loss at 2 years post-treatment (Fig. 3). More
than two thirds reported modifying their diet, adding fluid
to food to assist with swallowing, and avoiding specific
foods as strategies to manage their swallowing difficulties.
Twenty-five percent reported not requiring any strategies to
help with swallowing. Regarding strategies to avoid weight
loss, over one third reported not requiring any strategies to
Table 2 Toxicity, functional swallowing, participant-rated functional impact, and weight at 2 years post-treatment with AFRT-CB compared
with pretreatment and 6 months post-treatment
Outcome
measure
Component Pretreatment
[M (SD)]
6 months
post-treatment
[M (SD)]
2 years
post-treatment
[M (SD)]
Post-hoc Wilcoxon signed-rank/paired t-test
Pre- vs. 2 years 6 months vs. 2 years
Z/t p Z/t p
CTCAE Xerostomia 0 (0) 1.08 (0.7) 1.67 (0.5) -3.18 \0.01 -2.33 0.02
Dysphagia 0 (0) 0.92 (0.7) 1.6 (0.7) -3.13 \0.01 -2.82 0.01
RBHOMS 8.67 (0.78) 7.83 (0.4) 7.33 (0.8) -3.1 \0.01 -3.0 \0.01
MDADI Global 83.6 (17.5) 70 (21.7) 75 (33.2) 0.86 0.39 -1.0 0.32
Emotional 87.9 (9.3) 77.8 (18.4) 78.5 (18.4) 1.56 1.12 -0.28 0.78
Functional 86.2 (13.2) 78.3 (14.5) 81 (17.6) 1.43 0.15 -0.67 0.5
Physical 81.4 (16.2) 70.2 (12.8) 70.8 (18.2) 2.08 0.04 -0.23 0.78
FACT-H&N Physical (0–28) 24.5 (4.6) 22.3 (6.1) 23.9 0.94 0.35 -1.5 0.12
Social/family (0–28) 24.1 (4.9) 21.9 (7.7) 22.2 (6.1) 1.56 0.12 -0.43 0.66
Emotional (0–24) 20.1 (3) 21.3 (2.6) 20.5 (3.5) -0.31 0.76 0.48 0.63
Functional (0–28) 22.1 (4.2) 20.7 (5.8) 22.3 (5.5) 0.05 0.96 -1.93 0.05
Head/neck-specific (0–48) 38.5 (5.6) 31 (6.7) 35.8 (6.7) 1.56 0.12 -2.4 0.02
Overall (0–156) 129.7 (13.4) 120.4 (20.3) 123.8 (18) 1.89 0.06 -1.22 0.22
Weight (kg) 82.5 (24.3) 70.2 (20.2) 71.6 (21.5) 3.17 \ 0.01 -0.23 0.59
Italicized values refer to significant results
CTCAE Common Toxicity Criteria of Adverse Events version 3.0, RBHOMS Royal Brisbane Hospital Outcome Measure for Swallowing,
MDADI M. D. Anderson Dysphagia Inventory, FACT-H&N Functional Assessment of Cancer Therapy Additional Concerns for Head and Neck
Fig. 1 Frequency of patient-reported barriers to oral intake 2 years
after treatment with AFRT-CB
B. Cartmill et al.: Long-term Functional Outcomes and Patient Perspective 485
123
maintain their weight (Fig. 3). The remainder reported use
of a variety of strategies, including exercise to improve
their appetite, eating a high-protein high-energy diet, or
taking oral supplements as recommended by their dietician
during treatment (Fig. 3).
Discussion
The current study found a significant deterioration in sali-
vary and swallowing toxicity at 2 years post-treatment
when compared to pretreatment and 6 months post-treat-
ment levels. As would be expected, this ongoing toxicity
impacted functional swallowing, with the majority of the
current cohort limiting their diet to soft foods. The current
data support that further declines in swallowing function
2 years after the AFRT-CB protocol can be anticipated and
thus long-term monitoring of swallowing function in this
population is warranted.
While there may be an absence of data specifically
related to the AFRT-CB protocol outcomes at 2 years post-
treatment, results from other definitive nonsurgical treat-
ment regimens have reported an ongoing functional impact
on swallowing and nutrition long-term post-treatment
[31–35]. Studies have found that between 5 and 50% of
participants are able to tolerate a full diet without restric-
tions at 1–2 years post-treatment with previously examined
radiotherapy protocols for HNC [17, 36–38]. The preva-
lence rate for impaired function observed in the current
study is therefore at the high end (42%) of the expected
Table 3 Frequency of patient-reported barriers to oral intake in relation to body impairments, and activity limitations/participation restrictions
as classified by the ICF, reported by participants at 2 years post-treatment with AFRT-CB
Patient reported barrier % Impairment in body function Activity limitation/participation restriction
Dry mouth 92 Salivation Eating
Taste problems 75 Taste function Eating
Food gets stuck 75 Pharyngeal swallowing Eating
Appetite problems 58 Energy and drive (appetite) Looking after one’s health, eating
Cough with food/fluid 50 Pharyngeal swallowing Eating
Difficulty enjoying meals 50 Emotional functions or contextual factor Looking after one’s self, eating
Sticky saliva 42 Salivation Eating
Chewing difficulties 33 Chewing Eating
Ulcers 25 Oral swallowing Eating
Jaw stiffness 25 Mobility of joint functions Eating
Thrush 17 Oral swallowing Eating
Fatigue 17 Energy and drive (energy level) Carrying out daily routine
Painful swallowing 17 Sensation of pain (pain in head and neck) Eating
Sense of smell changed 8 Smell function Eating
Neck stiffness 8 Mobility of joint functions Eating
0
10
20
30
40
50
60
70
80
90
100
Modifiy diet Add fluid tofood
Avoidspecificfoods
Salivasubstitutes
Multipleswallows
Nostrategies-swallowing
Swallow strategy
Per
cen
tag
e
Fig. 2 Frequency of patient-reported strategies used to overcome
swallow-related side effects 2 years after treatment with AFRT-CB
0
1020
3040
50
6070
8090
100
Exerci
se
High pr
otein/en
ergy
diet
Oral s
upple
ments
Regular
weights
Use flu
ids
Midm
eal s
nack
s
No stra
tegie
s - w
eight
Weight strategy
Per
cen
tag
e
Fig. 3 Frequency of patient-reported strategies used to maintain
weight 2 years after treatment with AFRT-CB
486 B. Cartmill et al.: Long-term Functional Outcomes and Patient Perspective
123
long-term swallowing outcomes from other protocols.
Although not specifically assessing dietary tolerance but
perhaps an indicator of functional outcomes, concomitant
boost protocols have been associated with a greater inci-
dence of long-term dysphagia, as measured by incidence of
aspiration pneumonia, feeding tube dependence, or stric-
ture [39].
The long-term deficits in swallowing function observed
following definitive nonsurgical treatment for HNC have
been attributed to late treatment effects, including tissue
atrophy, oedema, and fibrosis [32–34]. Hence, the reason
for deterioration in toxicity and subsequent impact on
functional swallowing and weight in the current cohort
may be the result of similar late or chronic effects of the
AFRT-CB protocol. However, research has also demon-
strated that late reactions following radiotherapy treatment
are not only caused by the radiobiological dose to tissues
but can also be linked to the extent and duration of acute
cellular mucosal depletion as is found in accelerated and
hyperfractionated regimens [4]. Where such late mucosal
reactions occur in part as a consequence of a severe acute
reaction [40], this has been referred to as ‘‘consequential’’
late toxicity. The underlying premise of AFRT is that
through the use of smaller fraction sizes it is possible to
reduce the impact of tumour cell repopulation, thus
improving cell kill but without increasing late toxicity.
However, it is well recognised that this form of treatment
results in heightened acute toxicity [4] and, hence, the
potential for consequential late effects. Although it is
impossible to make any definitive statements regarding the
cause of the declining function observed in the current
study, it is possible that the factors contributing to the
observed decline in swallowing and salivary toxicity in the
current cohort may be a combination of both ‘‘true’’ and/or
‘‘consequential’’ late effects of treatment [4, 5].
The nature of the long-term swallowing deficits reported
in this study appears to be comparable to previous popu-
lations studied. Although the current study did not objec-
tively assess function using videofluoroscopy, 75% of
patients reported ‘‘food sticking in the throat,’’ and 50%
reported ‘‘coughing with food and/or fluid.’’ These patient
descriptions most likely relate to the presence of pharyn-
geal residue and penetration/aspiration which have been
identified as key physiological deficits present in the long
term following treatment in heterogeneous HNC popula-
tions studied [33, 34]. The current data, however, do differ
from most other radiotherapy research with respect to the
pattern of declining function in the long term, with the
prevalence of swallowing difficulty in the current cohort
observed to increase from 6 months to 2 years. This pattern
of declining function over time also differs from the gen-
eral pattern of improvement in swallowing outcomes
reported by Yu et al. [11] following AFRT. The differences
found between the results of the current study and those of
Yu et al. [11] could be attributed to the retrospective nature
of data collection and the use of a crude rating scale to
measure dysphagia in the Yu et al. [11] study. However, it
is equally acknowledged that currently there are minimal
data specific to the AFRT-CB population available for
comparison and further research is needed to confirm the
current pattern of long-term declining function as observed
in the current cohort.
Using the ICF framework, the functional swallowing
and ongoing barriers to oral intake reported by participants
at 2 years post-treatment were observed to primarily con-
tribute to activity limitation and participation restriction
related to eating. Previous studies have linked impairments
in body functions to activity limitations in eating, although
without formally using the ICF framework. Ku et al. [41]
reported that 90% of their heterogeneous HNC cohort who
received chemoradiation reported dry mouth (impairment
in body function) at 12 months post-treatment, and this
coincided with 100% alternating food and fluid boluses
(eating limitation) and more than 80% avoiding specific
foods in their diet (eating limitation). Oral pain, mouth
sores, taste changes, oral dryness, and loss of appetite have
previously been reported as side effects which heighten
awareness of functional swallowing difficulties [42, 43].
Long-term xerostomia has been postulated as having an
impact on functional swallowing by decreasing bolus
lubrication and increasing bolus transit time [34], and it
was reported by over 90% of the current cohort.
Fatigue and appetite were two patient-reported barriers
to oral intake that were classified as impairments to body
functions for energy and drive (appetite and energy level
subcategories). These impairments resulted in activity
limitations and participation restrictions in regard to
looking after one’s health and carrying out a daily routine,
as well as eating. Previous literature has reported these
impairments under social functioning and work and day-to-
day tasks [44]. One of the restrictions to using the ICF
framework is in the classification of enjoyment or pleasure
in regard to eating and drinking activity and participation,
which could be classified under emotional functioning or as
a contextual factor. Despite participants being able to
participate in eating and drinking activities, there is no
current classification that outlines whether participation is
enjoyable or not. For many HNC patients, not only is the
act of eating made difficult as a result of treatment side
effects, but enjoyment or pleasure from eating is also
impaired, possibly resulting in poor nutrition, weight loss,
and social isolation.
The current cohort described using a number of strate-
gies to facilitate eating, including dietary (modifying diet,
avoiding specific foods), mealtime (alternating food/fluid
boluses), and physiological (multiple swallows to clear
B. Cartmill et al.: Long-term Functional Outcomes and Patient Perspective 487
123
residue, using salivary substitutes to alleviate the impact of
dry mouth during meals) facilitators. Each individual
reported the use of multiple strategies to assist intake, and
those strategies that were most effective varied among the
patients. ‘‘Active planning’’ and the use of ‘‘trial and error’’
with respect to strategies regarding food selection, con-
sistency, preparation, caloric density, and the physical act
of eating have similarly been described in heterogeneous
HNC populations [43–45]. The information obtained from
further comprehensive study of patient strategies may help
in the future to further optimise patient adjustment to the
swallowing changes that continue in the long term after
treatment.
Despite worsening functional swallowing, and perhaps
as a result of these mealtime strategies, participants’ weight
remained stable between 6 months and 2 years post-treat-
ment. Interestingly, fewer participants reported strategies
to maintain their weight versus strategies to improve their
swallowing, and this may have had an impact on partici-
pants’ ability to regain lost weight between 6 months and
2 years post-treatment. In contrast, the lack of strategies to
maintain weight may reflect the patient’s perspective that
weight was no longer a concern. In the absence of data
regarding each patient’s personal goal weight, it is not
possible to determine how many chose to remain at the
lower post-treatment weight and how many were unable to
intentionally regain the weight they had lost.
Reflecting the decline in swallowing function and its
impact on activity and participation levels observed at
2 years, the patients’ self ratings for the physical compo-
nent of the MDADI were found to reveal a significant
deterioration between pretreatment and 2 years post-treat-
ment. The results of this specific patient-rated physical
domain of swallowing at 2 years post AFRT-CB are in
contrast with the previously reported data for heteroge-
neous HNC patients which showed improving global
function on the EORTC-QLQ-C30 scale by 12 months
post-treatment [13–17]. Furthermore, overall patient-rated
functional outcomes (using the FACT-H&N) have also
been found improve to pretreatment levels by 12 months
post-treatment following a hyperfractionated, accelerated
regimen [18]. Examination of the physical components of
the MDADI for the current cohort revealed a significant
long-term concern regarding the ongoing limitations to the
foods they could eat and increased effort and time to
complete meals.
Despite patients reporting some specific concerns, the
remaining data from the broader functioning domains of
the MDADI and FACT-H&N assessments revealed that
patients’ perceptions of their levels of general function had
returned to pretreatment levels by 2 years post-treatment.
This pattern of long-term adjustment has been found
previously [13–18]. In the current cohort, head and
neck–specific concerns such as cosmesis, voice and com-
munication, and the presence of pain significantly
improved from 6 months to 2 years post-treatment. The
results from the current study reveal that for patients who
underwent AFRT-CB, broadly speaking patient-rated
function continues an upward trajectory of improvement
post-treatment. In the absence of improvement in toxicity
and functional swallowing, this finding may be an indica-
tion of patient adjustment to the ongoing deficits caused by
HNC and its treatment [27, 46–48].
While the current study is the first to provide informa-
tion on long-term outcomes following an AFRT-CB pro-
tocol, the limitations of this study are acknowledged, with
small numbers restricting the ability to make generalisa-
tions about long-term function from this population. While
the aim of this study was to examine the functional out-
comes and explore the patient’s perspective of their treat-
ment and subsequent barriers to intake, the lack of
videofluoroscopic assessment at the 2-year time point does
not allow comment on long-term swallowing physiology.
Although not the focus of this study, the assimilation
toward pretreatment patient-rated function (as scored by
validated questionnaires), despite ongoing reports of body
function impairment, may also be related to the contextual
personal and environmental factors as well as premorbid
body functions of optimism and other temperament and
personality functions, outlined by the ICF. Factors such as
support and relationships, personal attitudes, and access to
ongoing services from health professionals may help some
individuals to consider their function in a more positive
way. Although not within the scope of the current study,
the functional impact that these long-term barriers to oral
intake have on spouses and family members is also
unknown. Often close family members are involved in food
selection and preparation and may report negative changes
in cooking, mealtime routines, reduced social eating with
family, and greater stress related to caring for their family
member who is a long-term HNC survivor. This notion of
‘‘third-party disability’’ [49] is an area that needs further
investigation, as well as the impact of contextual factors on
recovery and perception of impairment.
The current study has revealed the lasting impact of
AFRT-CB on salivary and swallowing function at 2 years
post-treatment, with the majority requiring ongoing dietary
restriction and reporting a significant negative impact on
the physical aspects of swallowing, which has contributed
to activity limitation and participation restriction in eating.
In general, weight that was lost from baseline to 6 months,
as a result of treatment side effects, had not been regained
2 years after treatment was completed. Several facilitatory
strategies to manage their impairments were reported by
participants. Overall, at 2 years post-treatment, participants
rated their global functioning as having returned to
488 B. Cartmill et al.: Long-term Functional Outcomes and Patient Perspective
123
pretreatment levels, possibly an indication of adjustment.
The long-term swallowing and nutritional dysfunction
highlights the need for ongoing speech pathology, dietetic,
social work, and psychology involvement in assisting
patients to return to their pretreatment oral intake, regain
weight lost as a result of treatment, and adapt and adjust to
potentially lifelong negative sequelae as a result of HNC
treatment.
Acknowledgment Funding for this research was obtained as PhD
scholarships through the Cancer Council Queensland and Cancer
Collaborative Group, Princess Alexandra Hospital.
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Bena Cartmill BSpPath (Hons)
Petrea Cornwell BSpPath (Hons), PhD
Elizabeth Ward BSpThy (Hons), Grad Cert Ed, PhD
Wendy Davidson BSc, Grad Dip Nutr Diet, Master Appl Sc (Res)
Sandro Porceddu BSc, MBBS (Hons), FRANZCR
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